*For correspondence. (e-mail: sanjayjachak@niper.ac.in) Challenges and opportunities in drug discovery from plants
Sanjay M. Jachak* and Arvind Saklani Department of Natural Products, National Institute of Pharmaceutical Education and Research, Sector-67, SAS Nagar, Punjab 160 062, India
Drug discovery from plants involves a multidiscipli- nary approach combining botanical, ethnobotanical, phytochemical and biological techniques. Plants con- tinue to provide us new chemical entitities (lead mole- cules) for the development of drugs against various pharmacological targets, including cancer, HIV/AIDS, malaria, Alzheimers disease and pain. Several natural- product drugs of plant origin are in clinical use, in- cluding paclitaxel, camptothecin-derived analogues, arteether, galanthamine, tiotropium to name a few, and some are undergoing Phase II and Phase III clinical trials. Although plant-based drug discovery program- mes continue to provide an important source of new drug leads, numerous challenges are encountered, in- cluding procurement and authentication of plant mate- rials, implementation of high-throughput screening bioassays and scale-up of bioactive lead compounds. At the same time, there are opportunities for India as it is rich in genetic resources and traditional know- ledge, which are key components for bioprospecting and value-addition.
Keywords: Bioprospecting, drug discovery, ethnobotany, ethnopharmacology, medicinal plants.
PLANTS have been the basis of many traditional medicine systems throughout the world for thousands of years and continue to provide mankind with new remedies. Plant- based medicines initially dispensed in the form of crude drugs such as tinctures, teas, poultices, powders, and other herbal formulations 1 , now serve as the basis of novel drug discovery. The process of drug discovery is multi- and inter- disciplinary. Apart from the core disciplines related to pharmaceutical research, classical sciences like taxonomy and the newer discipline ethnobotany have now become an integral part of drug discovery from plants. The plant- based indigenous knowledge was passed down from gene- ration to generation in various parts of the world throughout its history and has significantly contributed to the development of different traditional systems of medi- cine. The use of plants as medicines has involved the iso- lation of active compounds, beginning with the isolation of morphine from opium in the early 19th century 2 and subsequently led to the isolation of early drugs such as cocaine, codeine, digitoxin and quinine, of which some are still in use 3,4 . Isolation and characterization of phar- macologically active compounds from medicinal plants continue today. More recently, drug discovery techniques have been applied to the standardization of herbal medi- cines, to elucidate analytical marker compounds. It is estimated that around 250,000 flowering plant species are reported to occur globally. Approximately half (125,000) of these are found in the tropical forests. They continue to provide natural product chemists with invaluable compounds for development of new drugs. The potential for finding new compounds is enormous as till date only about 1% of tropical species have been studied for their pharmaceutical potential. The success of drug discovery from plants resulted principally in the develop- ment of anti-cancer and anti-bacterial agents. The success of anti-cancer drug development can be illustrated from the efforts of the National Cancer Institute (NCI), USA. In this effort, field explorations are largely guided by the so-called biodiversity or random collection approach, with ethnobotanical or ethnopharmacological information playing a minimal or no role. NCI launched its effort in 1955, and for the period 196082, about 114,000 extracts from an estimated 35,000 plant samples (representing 12,000 13,000 species) collected mostly from temperate regions of the world had been screened against a number of tumour systems 5 . A wide variety of compound classes were isolated and characterized. Clinically significant cancer chemotherapeutic agents that emerged from this pro- gramme included paclitaxel (Taxus brevifolia Nutt. and other Taxus sp., Taxaceae), hycamptamine (topotecan), CPT-11 and 9-aminocamptothecin. The latter three com- pounds are semi-synthetic derivatives of camptothecin (Camptotheca acuminata Decne., Nyssaceae) 6 . The pro- gramme was extended from 1986 to 2004, with an emphasis on global plant collections and screening against tumour cell cultures. Drug discovery from plants has evolved to include numer- ous interdisciplinary fields and various methods of analysis. The process typically begins with a botanist, ethnobotanist, ethnopharmacologist, or plant ecologist who collects and identifies the plants of interest. Collection may involve species with known biological activity for which active compound(s) have not been isolated or may involve taxa collected randomly for a large screening programme. It is necessary to respect the intellectual property rights of a given country where plants of interest are collected 7 . Phyto- REVIEW ARTICLE
CURRENT SCIENCE, VOL. 92, NO. 9, 10 MAY 2007 1252 chemists (natural product chemists) prepare extracts from the plant materials, subject these extracts to biological screening in pharmacologically relevant assays, and com- mence the process of isolation and characterization of the active compound(s) through bioassay-directed fractiona- tions. Molecular biology has become essential to medicinal plant drug discovery through the determination and imple- mentation of appropriate screening assays directed towards physiologically relevant molecular targets. Importance of medicinal plants in drug discovery Numerous methods have been utilized to acquire com- pounds for drug discovery, including isolation from plants and other natural sources, synthetic chemistry, combinatorial chemistry and molecular modelling 8,9 . Despite the recent interest in molecular modelling, combinatorial chemistry and other synthetic chemistry techniques by pharmaceutical companies and funding organizations, natural products and particularly medicinal plants, remain an important source of new drugs, new drug leads and new chemical entities (NCEs). According to Newman et al. 10 , 61% of the 877 small-molecule NCEs introduced as drugs worldwide during 19812002 was inspired by natural products. These include: natural products (6%), natural products derivatives (27%), synthetic compounds with natural products-derived pharmacophore (5%) and synthetic com- pounds designed from natural products (natural products mimic, 23%) 4,10 . Ten examples of successful drugs de- rived from plants (Figure 1) are briefly described here. Arteether (1) is a potent anti-malarial drug and is derived from artemisinin, a sesquiterpene lactone isolated from Artemisia annua L. (Asteraceae), a plant used in traditional Chinese medicine 11,12 . Galanthamine (2) is a natural product discovered through an ethnobotanical lead and first isolated from Galanthus woronowii Losinsk. (Amaryllidaceae) in Russia. Galanthamine is approved for the treatment of Alzheimers disease, slowing the process of neurological degeneration by inhibiting acetylcholine esterase as well as binding to and modulating the nicotinic acetylcholine receptor 13,14 . Tiotropium (3) has been released recently in the US for treatment of chronic obstructive pulmonary disease 15,16 . Tiotropium is an inhaled anticholinergic bro- nchodilator, based on ipratropium, a derivative of atro- pine, isolated from Atropa belladonna L. (Solanaceae) and other members of the Solanaceae family 17 . Morphine- 6-glucuronide (4) is a metabolite of morphine from Papaver somniferum L. (Papaveraceae), reported as an alternative pain medication with fewer side effects than morphine 18 . Exatecan (5) is an analogue of camptothecin isolated from Camptotheca acuminata Decne. (Nyssaceae) and being developed as an anticancer agent 4,19 . Vinflunine (6) is a modification of vinblastine from Catharanthus roseus G. Don (Apocynaceae) for use as an anticancer agent with improved efficacy 20 . Compounds (46) all are in phase III clinical trials 21 . Thus, from these three examples, it is evident that modifications of existing natural products can lead to NCEs and possible drug leads, from medicinal plants. (+)-Calanolide A (7) is a dipyranocoumarin compound isolated from Calophyllum lanigerum var. austrocoriaceum (Whitmore) P.F. Stevens (Clusiaceae), a Malaysian rain- forest tree 22,23 . (+)-Calanolide A is an anti-HIV drug with specific mechanism of action as a non-nucleoside reverse transcriptase inhibitor of type-1 HIV and is effective against AZT-resistant strains of HIV. It is currently un- dergoing phase II clinical trials 23,24 . Recently, (+)-calanolide A has been reported as an anti-tubercular agent. (+)- Calanolide A was consistently active (MIC 816 g/ml) against drug-susceptible strains of Mycobacterium tuber- culosis. Efficacy evaluations in macrophages revealed that (+)-calanolide A significantly inhibited intracellular replication of M. tuberculosis H37Rv at concentrations below the MIC observed in vitro. Preliminary mechanis- tic studies indicated that (+)-calanolide A rapidly inhibits RNA and DNA synthesis followed by inhibition of pro- tein synthesis. (+)-Calanolide A and related pyranocou- marins represent the first class of compounds identified to possess antimycobacterial and antiretroviral activities and thus, a new pharmacophore for anti-TB activity 25 .
Figure 1. Chemical structures of plant-derived drugs. REVIEW ARTICLE
CURRENT SCIENCE, VOL. 92, NO. 9, 10 MAY 2007 1253 The current emphasis of new drug discovery processes from plants is the development of products with new pharmacological modes of actions, apart from the known advantage of structural novelty. From India, three drugs qualify, i.e. flavopiridol (8), forskolin (9) and guggulsterone (10), on account of their modes of action. Flavopiridol is totally synthetic, but the basis of its novel flavonoid structure is a natural product, rohitukine. The latter iso- lated as the constituent responsible for anti-inflammatory and immunomodulatory activity from Dysoxylum binec- tariferum Hook. f. (Meliaceae), which is phylogenetically related to the Ayurvedic plant, Dysoxylum malabaricum Bedd., is used for rheumatoid arthritis. Flavopiridol was one of the over 100 analogues synthesized during structure activity studies, and was found to possess tyrosine kinase activity and potent growth inhibitory activity against a series of breast and lung carcinoma cell lines 26 . It also showed broad-spectrum in vivo activity against human tumour xenografts in mice, which led to its selection for preclini- cal and clinical studies by the NCI in collaboration with Hoechst. It is currently in 18 phase I and phase II clinical trials, either alone or in combination with other antican- cer agents, against a broad range of tumours, including leukaemias, lymphomas and solid tumours 27 . Forskolin, a labdane diterpenoid isolated from the Indian herb, Coleus forskohlii Briq., is a unique, potent, adenylate cyclase acti- vator. In view of the cyclic AMP-dependent effects pro- duced by forskolin, it was considered for development as an agent for the treatment of congestive cardiomyopathy, glaucoma and asthma. Later, several analogues were syn- thesized and structureactivity relationships developed. The semi-synthetic derivatives were approved for clinical use, mainly in the treatment of glaucoma 28 . The gum resin of Commiphora mukul (Stocks) Engl., commonly referred to as the Guggul tree, has been used in traditional Ayurvedic medicine for nearly 3000 years. It was reported to be effective in the treatment of several conditions, in- cluding obesity and disorders of lipid metabolism. An or- ganic extract of this gum resin, referred to as gugulipid, has been approved for use in India since 1987 for the treatment of hyperlipidaemia. Studies of patients receiving this therapy and experiments with rodent models have demonstrated that gugulipid effectively lowers serum low-density lipoprotein and triglyceride levels 29 . Guggul- sterone [4,17(20)-pregnadiene-3,16-dione], the active component of gugulipid, is largely responsible for anti- hyperlipidemic effects of this extract. The hepatic conver- sion of cholesterol to bile acids is an important mechanism for the elimination of excess dietary cholesterol. Bile acid biosynthesis and transport are regulated by the farnesoid X receptor (FXR), a member of the nuclear hormone re- ceptor gene superfamily. Thus, therapeutic strategies that target FXR represent a promising new approach for the treatment of hypercholesterolaemia. It has been reported that guggulsterone
is a highly efficacious antagonist of the FXR. Guggulsterone treatment decreases hepatic cho- lesterol in wild-type
mice fed with a high-cholesterol diet, but is not effective in FXR-null
mice. Thus, it was pro- posed that inhibition of FXR activation is the
basis for the cholesterol-lowering activity of guggulsterone 30 . Challenges in drug discovery from medicinal plants In spite of the success of drug discovery programmes from plants in the past 23 decades, future endeavours face many challenges. Natural products scientists and pharmaceutical industries will need to continuously im- prove the quality and quantity of compounds that enter the drug development phase to keep pace with other drug discovery efforts. The process of drug discovery has been estimated to take an average period of 10 years and cost more than 800 million dollars 31 . Much of this time and money is spent on the numerous leads that are discarded during the drug discovery process. It is estimated that only one in 5000 lead compounds will successfully ad- vance through clinical trials and be approved for use. In the drug discovery process, lead identification is the first step (Figure 2). Lead optimization (involving medicinal and combinatorial chemistry), lead development (includ- ing pharmacology, toxicology, pharmacokinetics, ADME and drug delivery), and clinical trials all take consider- able time. Different approaches to drug discovery from plants can be enumerated as: random selection followed by chemical screening, random selection followed by one or more bio- logical assays, follow-up of biological activity reports, follow-up of ethnomedical (traditional medicine) use of plants, use of appropriate plant parts as such in powdered form or preparation of enriched/standardized extracts (herbal product development), use of a plant product, bio- logically potent but beset with other issues, as a lead for
Figure 2. Drug discovery process from plants. REVIEW ARTICLE
CURRENT SCIENCE, VOL. 92, NO. 9, 10 MAY 2007 1254 further chemistry, and single new compounds as drugs. The objective of the latter approach is the targetted isola- tion of new bioactive plant products, i.e. lead substances with novel structures and novel mechanisms of action. This approach has provided a few classical examples, but the problem most often encountered here is not enough availability. The problem of availability can be overcome by semi-synthesis/synthesis or using tissue-culture tech- niques (by genetically modifying the biosynthetic path- way of the compound of interest). The approach of herbal drug development is associated with several problems. Crude herbs/plants (various plant parts and exudates) are mostly formulated as tablet and capsule, and to some extent as oral liquid preparations. These dosage forms are not successful due to problems encountered in absorption, therapeutic efficacy and poor compliance. Tablet or capsule dosage form requires pow- dering of crude herbs and particle size affects the process of blending, compression and filling. In addition, homo- geneity is difficult to achieve due to the handling of large bulk quantities, high moisture content and inherent nature of raw materials (crude drug). Crude extracts are difficult to formulate in solid dosage forms due to their hygro- scopic nature, poor solubility and stickiness. As drug discovery from plants has traditionally been time-consuming, faster and better methodologies for plant collection, bioassay screening, compound isolation and compound development must be employed 32 . Innovative strategies to improve the process of plant collection are needed, especially with the legal and political issues sur- rounding benefit-sharing agreements 33,34 . The design, deter- mination and implementation of appropriate, clinically relevant, high-throughput bioassays are difficult proc- esses for all drug discovery programmes 35,36 . Although the design of high-throughput screening assays can be challenging 37 , once a screening assay is in place, com- pound and extract libraries can be tested for biological activity. The common problem faced during screening of extracts is solubility and the screening of extract libraries is many times problematic, but new techniques including pre-fractionation of extracts can alleviate some of these issues 4,32 . Challenges in bioassay screening remain an important issue in the future of drug discovery from me- dicinal plants. The speed of active compound isolation can be increased using hyphenated techniques like LC- NMR and LC-MS. Development of drugs from lead com- pounds isolated from plants, faces unique challenges. Natural products, in general, are typically isolated in small quantities that are insufficient for lead optimiza- tion, lead development and clinical trials. Thus, there is a need to develop collaborations with synthetic and medicinal chemists to explore the possibilities of its semi-synthesis or total synthesis 9,38,39 . One can also improve the natural products compound development by creating natural pro- ducts libraries that combine the features of natural products with combinatorial chemistry. After considering all these issues, we would like to discuss the Indian scenario with respect to challenges in drug discovery from plants. Indian scenario India represented by rich culture, traditions and natural biodiversity, offers a unique opportunity for drug discovery researchers. This knowledge-based country is well recogni- zed for its heritage of the worlds most ancient traditional system of medicine, Ayurveda. Even, Dioscorides (who influenced Hippocrates) is thought to have taken many of his ideas from India 40 . We in India have two (Eastern Himalaya and the Western Ghats) of the 18 hotspots of plant biodiversity in the world. Interestingly, we are sev- enth among the 16 megadiverse countries, where 70% of the worlds species occurs collectively. We are rich in our own flora, i.e. endemic plant species (5725 angiosperms, 10 gymnosperms, 193 pteridophytes, 678 bryophytes, 260 liverworts, 466 lichens, 3500 fungi and 1924 algae) 41 . Unfortunately, due to various reasons including inacces- sibility of some tough terrains, only 65% flora of the country have been surveyed so far. With the dwindling population of taxonomists and rare introduction of youngsters in this field, it might take an- other 2030 years with the current pace to survey the complete flora of the country. Now the question before us is, could we assess the pharmaceutical potential of all the floristic components that we know? The answer is no. Realizing that we have approximately 17,500 species of higher plants, 64 gymnosperms, 1200 pteridophytes, 2850 bryophytes, 2021 lichens, 15,500 fungi and 6500 algae at our disposal, surprisingly, hardly a few institutions like Central Drug Research Institute, Lucknow with its con- certed efforts could test a few plants and have published results on 3488 species of plants for limited indications in almost 28 years 42 between 1968 and 1996. This resulted into some promising leads that were later developed as drugs, viz. bacoside, the memory enhancer from Bacopa monnieri (L.) Penn.; picroliv, the hepatoprotective from Picrorhiza kurroa Benth., curcumin, the anti- inflammatory from Curcuma domestica Valeton, consap, the contraceptive cream from Sapindus mukorossi Gaertn., etc. Other CSIR laboratories and some private pharma- ceutical companies have also made some efforts in this direction. However, assessing the pharmaceutical poten- tial of our whole flora even for the important disease in- dications may take several decades. The reason could be the availability of source plant material, expertise to authen- ticate the taxa, developing enough suitable in vitro screens for all indications, reproducibility of results and so on. Whatever the case may be, can we afford to wait any longer to evaluate our flora for its medicinal efficacy? The procedure for access to biological resources now is somewhat tedious. According to The Biological Diver- REVIEW ARTICLE
CURRENT SCIENCE, VOL. 92, NO. 9, 10 MAY 2007 1255 sity Rules, 2003 of the Govt of India (notified on 24 March 2004), any person who is not a citizen of India (foreigner, non-resident Indian) or any foreign corporate, seeking approval of the Authority (National Biodiversity Authority NBA) for access to biological resources and associated knowledge for research or for commercial utilization shall make an application in Form I as given in schedule. Every application shall be accompanied by a fee of Rs 10,000. The Authority on being satisfied with the merit of the application, may grant the approval as far as possible within a period of six months of receipt of the same. One has to specify each time the quantity to be col- lected of exact species, quantum of monetary and other incidental benefits and also guarantee to deposit a refer- ence sample of the biological material sought to be ac- cessed with the repositories identified and submitting to the Authority a regular status report of research and other developments 43 . However, according to the Biodiversity Act 2002, a citizen of India need not seek permission of NBA for the access of biodiversity, but one has to inform the respective State biodiversity boards for collection of plant material. As the process of plant-based drug discov- ery involves continuous collection of plant material from different places at various point of time, it is rather im- practical to wait for obtaining permission each time. At the same time, the authorities cannot also give blanket permission for any collector. We have to find a way out. A lot of field experience and wide floristic knowledge is required if one wants to go for the random collection pro- gramme required for preliminary screening. Once found active, target plant collection in bulk quantity may be a problem due to its threatened status in some cases, or biomass and scattered distribution in others. Authentication of plant material is an important and most crucial factor in plant-based drug discovery. This needs to be supported by a set of suitable voucher specimens of the target spe- cies authenticated by a botanist and then deposited with a recognized herbarium. In the absence of vouchers, it is next to impossible to remember the location/ phytogeographical conditions and time/season of collec- tion of the exact plant material for repeat studies. Repro- ducibility of the results depends on various other factors too. Proper collection procedures need to be laid and docu- mented. Collection practices should ensure long-term survival of wild populations and their associated habitats. Management plans for collection should provide a framework for setting sustainable harvest levels and de- scribe appropriate collection practices that are suitable for each medicinal plant species and plant part used 44 . This should also include good field documentation, use of global positioning system to pinpoint site locations, map- ping of sites and availability of good supporting data- bases. In case of tree or shrub species where root or bark is being used or found active, phytochemical and biologi- cal evaluation of leaves, twigs, stems, flowers and fruits must be done in order to ensure sustainable utilization of the plant. Potential herbs have an added advantage over others, as the bulk quantity and quality of target material can easily be assured through cultivation using Good Ag- ricultural Practices (GAP) and Good Collection Practices (GCP). Another important issue here is the pharmaceutical evaluation of rare or endangered species. According to the Govt of India notification (Notification No. 2(RE- 98)/19972002), 29 taxa have been banned and the export of plants, plant portions and their derivatives and extracts obtained from the wild is prohibited 45 . These species, in- cluding other Red-listed threatened species, following the current IUCN norms, cannot be collected from the wild and in turn remain dead for science as far as their phar- maceutical potential is concerned. Interestingly, many of these species do find mention in our traditional Indian systems/tribal systems of medicine. After collection, the drying procedures that vary for different plant materials, may alter the chemical proper- ties of the material. The commonly employed drying pro- cedures are sun- and/or shade-drying. Right kind of packaging procedures adopted in order to avoid fungal in- fection also need to be carefully worked out before trans- portation of material to the laboratory. Processing of plant materials mainly includes pulverization and then preparation of extracts. Various extracts such as hexane, chloroform, ethyl acetate, n-butanol and ethanol or 70% ethanol are generally prepared for chemoprofilings as well as for biological screening. Opportunities Bioprospecting demands a number of requirements which should be co-coordinated, such as team of scientific ex- perts (from all the relevant interdisciplinary fields) along with expertise in a wide range of human endeavours, in- cluding international laws and legal understanding, social sciences, politics and anthropology. In the Indian context, Ayurveda and other traditional systems of medicine, rich genetic resources and associated ethnomedical knowledge are key components for sustainable bioprospecting and value-addition processes. For drug-targetted bioprospect- ing an industrial partner is needed, which will be instru- mental in converting the discovery into a commercial product. Important in any bioprospecting is the drafting and signing of an agreement or Memorandum of Under- standing that should cover issues on access to the genetic resources (biodiversity), on intellectual property related to discovery, on the sharing of benefits as part of the process (short term), and in the event of discovery and commercialization of a product (long term), as well as on the conservation of the biological resources for the future generations. When ethnobotanical or ethnopharmacological approach is utilized, additional specific requirements that relate to prior informed consent, recognition of Indige- REVIEW ARTICLE
CURRENT SCIENCE, VOL. 92, NO. 9, 10 MAY 2007 1256 nous Intellectual Property and Indigenous Intellectual Property Rights as well as short- and long-term benefit sharing need to be taken into account 46,47 . In order to screen thousands of plant species at one go for as many bioassays as possible, we must have a collec- tion of a large number of extracts. Globally, there is a need to build natural products extract libraries. The extract libraries offer various advantages, such as reduction in cost and time for repeat collection of plants and availabi- lity of properly encoded and preserved extracts in large numbers for biological screening in terms of high-throughput screenings and obtaining hits within a short period. In India, though some institutions have small plant extract libraries, they are not in public domain. The only information is available from Nicholas Piramal India Ltd. (NPIL), one of the major pharma players in India. NPIL has built up a plant extract library having 6000 extracts prepared from around 2300 plant species collected from all over India 48 . Such libraries could serve as a powerful tool and source of extracts to be screened for biological activities using high-throughput assays. Glimpse of Indian initiatives on plant prospecting Various government agencies like Department of Bio- technology (DBT), Council of Scientific and Industrial Research (CSIR) and Department of Ayurveda, Unani, Siddha and Homeopathy (AYUSH), Ministry of Health and Family Welfare have initiated efforts on bioprospect- ing. DBT initiated the network programme on Bio- prospecting of biological wealth using biotechnological tools during the 9th plan involving 13 institutions. The ob- jectives of the DBT programme were characterization of biodiversity in different agro-ecological regions, bio- resources mapping, inventorization and monitoring of biological diversity, characterization and conservation of Himalayan endangered species, including medicinal and aromatic plants, and bioprospecting of molecules and genes for product development. The leads obtained from the first phase of bioprospecting have been taken up for detailed investigation, with a focus on product and process development and commercialization. CSIR has initiated a coordinated programme on drug discovery with a network of 19 CSIR laboratories and other R&D institutions working in the field of traditional medicines as well as universities. The programme was initiated in 1996, and aims at discovering new bioactive molecules from plants, fungi, microbes, insects, etc. using new technologies. The Planning Commission sponsored the New Millennium Indian Technology Leadership Initia- tive (NMITLI), one of the most innovative bioprospecting programmes. NMITLI started a major herbal drug devel- opment programme for developing effective herbal reme- dies for diabetes, arthritis and hepatic disorders, which has shown highly encouraging results within a short period of time. The Ministry of Health and Family Welfare, Govt of India initiated two important task-force programmes re- lating to creation of Traditional Knowledge Digital Li- brary and designing a Traditional Knowledge Resource Classification (TKRC). The TKRC has information on 5000 subgroups and the structure of TKRC is compatible with the International Patent Classification. TKRC will help enhance the quality of patent examinations by facili- tating the patent examiners to access pertinent information on traditional knowledge in an appropriately classified form 49 . Conclusion As evident from the above discussion, nature is the best combinatorial chemist and possibly has answers to all diseases of mankind. Till now, natural products com- pounds discovered from medicinal plants (and their ana- logues thereof) have provided numerous clinically useful drugs. In spite of the various challenges encountered in the medicinal plant-based drug discovery, natural products isolated from plants will still remain an essential compo- nent in the search for new medicines. The fact that only about one-tenth of the flowering species occurring glob- ally are investigated for their pharmaceutical potential, can be the obvious advantage to begin with plant/ medicinal plant-based drug discovery programmes. The diverse genetic resources and associated rich traditional knowledge available in India form the strong basis for bioprospecting. Proper utilization of these resources and tools in bioprospecting will certainly help in discovering novel lead molecules from plants by employing modern drug discovery techniques and the coordinated efforts of various disciplines.
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Received 11 March 2006; revised accepted 15 February 2007
DAO 2004-01 IRR FOR RA 9147 (Act Providing For The Conservation and Protection of Wildlife Resources and Their Habitats, Appropriating Funds Therefore and For Other Purposes)